Long noncoding RNA XIST: a novel independent prognostic biomarker for patients with ABC-DLBCL receiving R-CHOP treatment.

ABSTRACT

Approximately one-third of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) cases were unresponsive to standard first-line therapy; thus, identifying biomarkers to evaluate therapeutic efficacy and assessing the emergence of drug resistance is crucial. Through early-stage screening, long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) was found to be correlated with the R-CHOP treatment response. This study aimed to clarify the characteristics of XIST in ABC-DLBCL. The expression level of XIST in 161 patients with ABC-DLBCL receiving R-CHOP therapy was examined via RNA in situ hybridization, and the association between XIST expression and clinicopathological features, treatment response and prognosis was analyzed in the study cohort and validated in the Gene Expression Omnibus cohort. Cell biological experiments and bioinformatics analyses were conducted to reveal aberrant signaling. The proportion of complete response in patients with high XIST expression was lower than that in patients with low XIST expression (53.8% versus 77.1%) (P = 0.002). High XIST expression was remarkably associated with the characteristics of tumor progression and was an independent prognostic element for overall survival (P = 0.039) and progression-free survival (P = 0.027) in ABC-DLBCL. XIST was proven to be involved in m6A-related methylation and ATF6-associated autophagy. XIST knockdown repressed ABC-DLBCL cellular proliferation by regulating Raf/MEK/ERK signaling. High XIST expression was associated with ABC-DLBCL tumorigenesis and development and contributed to R-CHOP treatment resistance. XIST may be a promising signal to predict ABC-DLBCL prognosis.